Peptide receptor radionuclide therapy for advanced gastroenteropancreatic neuroendocrine tumors — from oncology perspective

Peptide Receptor Radionuclide Therapy (PRRT) is a form of molecular targeted therapy which is performed by using a small peptide (somatostatin analogue — SSA) that is coupled with a radionuclide beta emitting radiation. PRRT is a nuclear medicine for the systemic treatment of non-resectable, metastasized well/moderately differentiated, neuroendocrine tumours (NET) with overexpression of somatostatin receptor. These types of tumours include gastroenteropancreatic neoplasm (GEP-NENs), e.g. arising from the small bowel (often called carcinoid tumours), the pancreas, duodenum or stomach, but also from the large bowel or the lung and many other tissues (so called diffuse neuroendocrine system). The goal of PRRT is irradiation of tumour cells, via direct binding into specific receptor, somatostatin receptors (SSTR) family, overexpressed on the cell membrane of the primary tumours as well as on the metastasis. Over many years of clinical use of PRRT with 90Y and current with 177Lu DOTA conjugated somatostatin analogues proved to be efficient therapy option for NETs, with tumour responses, base on radiological evaluation. Also, a clinical response with symptoms relief and improvement in quality of life based on standard EORTC questioners is seen. Additional, common NET biomarker reduction and, ultimately, an impact on overall survival (OS) of patients with advanced non-resectable often progressive NEN can be expected. PRRT with 90Y or 177Lu-labelled peptides is generally well tolerated by most of the patients. The acute side effects (Adverse Events — AEs) are usually mild; most of them are related to the co-administration of amino acids (AA), such as nausea and vomiting. Others are related to the radioisotopes, such as fatigue or the exacerbation of endocrine syndromes, which are very rarely and they occurs, only in patients with functional tumours and large tumours burden. Chronic and permanent damage has an effect on target organs, particularly the kidneys and the bone marrow, which are generally mild. Currently, when 177Lu DOTATATE is used, the potential risk to kidney damage is significantly reduced, compared to the previous usage of 90Y labelled analogues. Up to now, kidney and bone marrow toxicity limits the dose of radioactivity of PRRT